HBO regulates the Warburg effect of hypoxic HCC cells through miR-103a-3p/TRIM35.

BACKGROUND: There are a lot of studies on the treatment of tumors with hyperbaric oxygen, while most of them are in breast cancer, prostate cancer and so on. However, there are still few studies on hyperbaric oxygen in treating hepatocellular carcinoma (HCC). According to the current data, hyperbaric oxygen is an effective means to intervene in tumors. The Warburg effect is a unique marker of glucose metabolism in tumors related to hypoxia, making it possible for hyperbaric oxygen to interfere with the tumor through the Warburg effect. METHOD: We used the hypoxia/hyperbaric oxygen(HBO)-exposed HCC cells for in vitro studies. Glucose uptake, lactic acid, and adenosine triphosphate (ATP) assessed the Warburg effect. The expression of miR-103a-3p in HCC was detected by using qRT-PCR. The effect of miR-103a-3p/TRIM35 expression level on the cells was measured using the CCK8 method and flow cytometry. The molecular biological mechanism of miR-103a-3p in HCC was examined using the luciferase reporter, MS2-RIP assays. RESULT: HBO inhibited the Warburg effect in hypoxic HCC cells. HBO suppressed the expression of miR-103a-3p in hypoxic HCC cells, and miR-103a-3p inhibited the expression of TRIM35 in hypoxic HCC cells. With HBO exposure, miR-103a-3p/TRIM35 regulated the Warburg effect of hypoxic HCC cells. CONCLUSION: These findings reveal that HBO regulates the Warburg effect of hypoxic HCC cells through miR-103a-3p/TRIM35 and inhibits tumor growth.

E2F1 Mediates Traumatic Brain Injury and Regulates BDNF-AS to Promote the Progression of Alzheimer's Disease.

Traumatic brain injury (TBI) is one of the important risk factors for the development of Alzheimer's disease (AD). However, the molecular mechanism by which TBI promotes the progression of AD is not elucidated. In this study, we showed that the abnormal production of E2F1 is a major factor in promoting the neuropathological and cognitive deterioration of AD post-TBI. We found that repeated mild TBI can aggravate the neuropathology of AD in APP/PS1 mice. At the same time, the co-expression of E2F1 and beta-site APP cleaving enzyme 1 (BACE1) was upregulated when the mouse hippocampus was dissected. BACE1 is recognized as a rate-limiting enzyme for the production of Aß. Here, we speculate that E2F1 may play a role in promoting BACE1 expression in AD. Therefore, we collected peripheral blood from patients with AD. Interestingly, there is a positive correlation between E2F1 and brain-derived neurotrophic factor-antisense (BDNF-AS), whereas BDNF-AS in AD can promote the expression of BACE1 and exhibit a neurotoxic effect. We established a cell model and found a regulatory relationship between E2F1 and BDNF-AS. Therefore, based on our results, we concluded that E2F1 regulates BDNF-AS, promotes the expression of BACE1, and affects the progression of AD. Furthermore, E2F1 mediates the TBI-induced neurotoxicity of AD.

Bone Marrow Mesenchymal Stem Cell-derived Exosomal microRNA- 99b-5p Promotes Cell Growth of High Glucose-treated Human Umbilical Vein Endothelial Cells by Modulating THAP Domain Containing 2 Expression.

INTRODUCTION: Bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) may function as novel candidates for treating diabetic wounds due to their ability to promote angiogenesis. MATERIALS AND METHODS: This study investigated the effects of BMSC-exos on the growth and metastasis of human umbilical vein endothelial cells (HUVECs) treated with high glucose (HG). The exosomes were separated from BMSCs and identified. The cell phenotype was detected by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and 5-ethynyl-2'-deoxyuridine, wound healing, and transwell assays, while the number of tubes was measured via tube formation assay. RESULT: The RNA and protein expression levels were studied using reverse transcription-quantitative polymerase chain reaction and western blotting, whereas integration of microRNA-99b-5p (miR-99b-5p) with THAP domain containing 2 (THAP2) was confirmed via dual-luciferase reporter and RNA pull-down assays. Results of transmission electron microscopy, nanoparticle tracking analysis, and laser scanning confocal microscopy revealed that exosomes were successfully separated from BMSCs and endocytosed into the cytoplasm by HUVECs. Similarly, BMSC-exos were found to promote the growth of HG-treated HUVECs, while their growth was inhibited by suppressing miR-99b-5p. THAP2 was found to bind to miR-99b-5p, where THAP2 inhibition reversed the miR-99b-5p-induced effects on cell growth, migration, and tube numbers. CONCLUSION: In conclusion, miR-99b-5p in BMSC-exo protects HUVECs by negatively regulating THAP2 expression.

Effects of extracellular vesicles from adipose-derived stem cells on human keloid fibroblasts via the SOCS1/JAK2/STAT3 pathway.

BACKGROUND: Keloid represents a benign skin tumor with many cancer-like features. Extracellular vesicles (EVs) derived from human adipose-derived stem cells (hADSCs) play a role in cell migration of multiple diseases. AIMS: This study aimed to investigate the impact of hADSC-EVs on human keloid fibroblasts (HKFs). METHODS: hADSCs were cultured to the 3rd generation, and subsequently assessed for their osteogenic, adipogenic, and chondrogenic differentiative abilities using flow cytometry, alizarin red, oil red O, and alcian blue staining techniques. hADSC-EVs were isolated through ultracentrifugation and subsequently identified. HKFs at the 3rd generation were subjected to treatment with hADSC-EVs to observe their endocytosis of EVs by immunofluorescence. CCK-8, wound healing, and Transwell assays were performed to test HKF proliferation and migration. The levels of autophagy proteins, collagens, and Janus kinase 2 (JAK2) and Signal Transducer and Activator of Transcription 3 (STAT3) were determined through Western blot analysis. Suppressor of cytokine signaling 1 (SOCS1) expression was determined by RT-qPCR and Western blot. RESULTS: hADSC-EVs were successfully isolated from hADSCs. PKH67-labeled hADSC-EVs were observed to be endocytosed by HKFs, resulting the inhibition of HKF proliferation, migration, as well as a reduction in collagen deposition. hADSC-EVs carried SOCS1 into HKFs to suppress HKF autophagy. SOCS1 downregulation in hADSC-EVs partially nullified the inhibitory effect of hADSC-EVs on HKFs. hADSC-EV-carried SOCS1 inhibited the activation of the JAK2/STAT3 pathway. JAK2/STAT3 pathway activation partially abrogated the suppression of hADSC-EVs on the proliferation, migration, and collagen deposition of HKF. CONCLUSION: hADSC-EVs carried SOCS1 into HKFs and suppressed HKF autophagy, proliferation, migration, and collagen deposition by inactivating the JAK2/STAT3 pathway.

miR-224-5p acts as a tumour suppressor and reverses the resistance to BRAF inhibitor in melanoma through directly targeting PAK4 to block the MAPK pathway.

miR-224-5p has been shown to play both an oncogene and tumour suppressor role in many human tumours. However, the role and molecular mechanism of miR-224-5p in cutaneous melanoma remains unclear. miR-224-5p levels were downregulated in melanoma tissue, and low miR-224-5p expression was an independent risk factor for melanoma patients. miR-224-5p blocked proliferation, epithelial-to-mesenchymal transition (EMT), invasion, migration in BRAF wild-type melanoma cell, and overcome acquired BRAFi resistance in VMF-resistant melanoma cells. miR-224-5p exerted its role by directly repressing PAK4 to block the downstream CRAF/MEK/ERK pathways. We demonstrated that miR-224-5p inhibited melanoma growth and metastasis in vivo though xenograft tumor and pulmonary metastasis assay. Thus, miR-224-5p/PAK4-mediated CRAF/MEK/ERK pathways have therapeutic potential in melanoma treatment.

MiR-29a-3p negatively regulates circulating Tfh memory cells in patients with Graves' disease by targeting ICOS.

MicroRNAs (miRNAs) are small endogenous noncoding RNAs that regulate genome expression posttranscriptionally and are involved in autoimmune diseases. Previous studies have indicated that follicular helper T (Tfh) cells play a critical role in the pathogenesis of Graves' disease (GD). However, the molecular mechanisms that contribute to circulating Tfh memory cell response in GD patients remain incompletely understood. This study aimed to investigate the role of miRNAs on circulating Tfh memory cells in GD patients. Herein, our data showed that the proportion of circulating Tfh memory cells, the transcript levels of IL-21, and the plasma concentrations of IL-21 were increased in the peripheral blood from GD patients. We also found that inducible co-stimulator (ICOS) expression, an important molecule expressed on Tfh cells, were significantly augmented in the peripheral blood mononuclear cells (PBMCs) from GD patients and positively correlated with the percentage of circulating Tfh memory cells and the transcript levels of IL-21 in GD. Intriguingly, miRNA sequencing screened miR-29a-3p expression was downregulated and inversely correlated with ICOS expression and the frequency of circulating Tfh memory cells in patients with GD. Luciferase assay demonstrated that ICOS was the direct target gene of miR-29a-3p, and miR-29a-3p could inhibit ICOS at both transcriptional and translational levels. Overexpression of miR-29a-3p reduced the proportion of circulating Tfh memory cells. Moreover, miR-29a-3p expression negatively correlated with serum concentrations of TSH receptor antibody (TRAb) in GD patients. Collectively, our results demonstrate that miR-29a-3p emerges as a post-transcriptional brake to limit circulating Tfh memory cell response in GD patients and may be involved in the pathogenesis of GD.

Novel lncRNA SNHG16 Promotes the Growth and Metastasis of Malignant Melanoma by Regulating miR-205-5p/PAK2 Axis.

Background: Long non-coding RNAs (lncRNAs) play an key role in the biological processes of various malignant tumors. SNHG16 has been confirmed to be associated with the progression of various cancers. However, function and molecular mechanism of SNHG16 in melanoma have not been studied by scholars. Methods: The expression of SNHG16 in melanoma tissues were detected by using qRT-PCR. Melanoma cases from The Cancer Genome Atlas (TCGA) and GEO#GSE15605 were included in this study. CCK-8 assay, EdU assay, transwell and scratch wound assay were used to explore the role of SNHG16 in melanoma cells. Luciferase reporter assays and RNA pull-down assay were used to explore the molecular mechanism of SNHG16 in melanoma. Results: Here, we found that SNHG16 was up-regulated in melanoma. SNHG16 enhances the growth and metastasis of melanoma. SNHG16 can promote the expression of P21-activated kinases 2 (PAK2) by sponging miR-205-5p. PAK2 is the target gene of miR-205-5p. We demonstrated that SNHG16 promotes the metastasis and growth of melanoma through miR-205-5p/PAK2 axis. Conclusion: This study firstly confirmed the role and mechanism of SNHG16 in the occurrence and development of melanoma. Therefore, SNHG16 may become a key point in the diagnosis, prognosis and treatment of melanoma patients in the future.

LncRNA BDNF-AS as ceRNA regulates the miR-9-5p/BACE1 pathway affecting neurotoxicity in Alzheimer's disease.

INTRODUCTION: The long non-coding RNA Brain-derived nutritional factor anti-sense RNA (BDNF-AS) is a type of anti-sense RNA that has been proven to play a crucial role in the occurrence and development of certain nervous system disorders. However, the role and molecular mechanism of BDNF-AS in Alzheimer's disease (AD) have not been elucidated yet. METHODS: Peripheral blood samples were collected from outpatients with AD as well as from normal elderly individuals in the community, and the expression of BDNF-AS was analysed using quantitative reverse transcription-polymerase chain reaction. An in vitro model was constructed, and the effect of BDNF-AS expression level on the cells was measured using the CCK8 method and flow cytometry. The molecular biological mechanism of BDNF-AS in AD was examined using the luciferase reporter, MS2-RIP, and RNA pulldown assays. RESULT: We found that the expression of BDNF-AS was elevated in the peripheral blood of patients with AD and that increased BDNF-AS expression may be associated with the cognitive status of such patients. The results confirmed that BDNF-AS could promote neurotoxicity in the in vitro model. Then, we uncovered that BDNF-AS promotes the expression of BACE1 through the competitive binding of miR-9-5p, thereby promoting amyloid deposition. Finally, through the Morris water maze, we found that the high expression of BDNF-AS promoted cognitive impairment in AD mice. CONCLUSION: The obtained results suggest that BDNF-AS plays a crucial role in the occurrence and development of AD. As a new pathogenic gene of AD, BDNF-AS may be used as a therapeutic target or as a prognostic marker in patients with AD.

Long non-coding RNA ZFAS1 promotes pancreatic cancer proliferation and metastasis by sponging miR-497-5p to regulate HMGA2 expression.

The lncRNA ZFAS1 plays a carcinogenic regulatory role in many human tumours, but it is rarely reported in pancreatic cancer. We identify the role and molecular mechanisms of ZFAS1 in pancreatic cancer. The expression of ZFAS1, miR-497-5p and HMGA2 in pancreatic cancer tissues was detected by qRT-PCR. Pancreatic cancer data in The Cancer Genome Atlas were also included in this study. CCK8, EdU, transwell and scratch wound assays were used to investigate the biological effects of ZFAS1 in pancreatic cancer cells. MS2-RIP, RNA pull-down, RNA-ChIP and luciferase reporter assays were used to clarify the molecular biological mechanisms of ZFAS1 in pancreatic cancer. The role of ZFAS1 in vivo was also confirmed via xenograft experiments. ZFAS1 was overexpressed in pancreatic cancer tissues. ZFAS1 promoted the growth and metastasis of pancreatic cancer cells, and miR-497-5p acted as a tumour suppressor gene in pancreatic cancer by targeting HMGA2. We also demonstrated that ZFAS1 exerts its effects by promoting HMGA2 expression through decoying miR-497-5p. We also found that ZFAS1 promoted the progression of pancreatic cancer in vivo by modulating the miR-497-5p/HMGA2 axis. In conclusion, this study revealed a new role for and the molecular mechanisms of ZFAS1 in pancreatic cancer, identifying ZFAS1 as a novel target for the diagnosis and treatment of pancreatic cancer.

Exosomal miR-106b-5p derived from melanoma cell promotes primary melanocytes epithelial-mesenchymal transition through targeting EphA4.

BACKGROUND: Cancer-secreted exosomal miRNAs regulates the biological processes of many tumours. The serum level of exosomal miR-106b-5p is significantly increased in melanoma patients. However, the role and molecular mechanisms of exosomal miR-106b-5p in melanoma remains unclear. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-106b-5p and EphA4 in melanoma tissues. Transmission electron microscopy (TEM) and western blotting were used to identify exosome. QRT-qPCR and Cy3-labelled miR-106b-5p were used to demonstrated the transmission of melanoma cell-secreted exosomal miR-106b-5p. Western blotting, Immunofluorescence, adhesion, transwell and scratch wound assay were used to explore the role of exosomal miR-106b-5p in melanocytes. Luciferase reporter assays and RNA-Chromatin Immunoprecipitation (ChIP) assay were used to confirm whether erythropoietin-producing hepatocellular carcinoma receptor A4 (EphA4) was a direct target of miR-106b-5p. RESULTS: We found that miR-106b-5p levels were increased in melanoma tissue, and high miR-106b-5p expression is an independent risk factor for the overall survival of patients with melanoma. miR-106b-5p is enriched in melanoma cell-secreted exosomes and transferred to melanocytes. Exosomal miR-106b-5p promotes the epithelial-to-mesenchymal transition (EMT), migration, invasion and adhesion of melanocytes. Exosomal miR-106b-5p exerted its role by targeting EphA4 to activate the ERK pathway. We demonstrated that exosomal miR-106b-5p promoted melanoma metastasis in vivo through pulmonary metastasis assay. CONCLUSIONS: Thus, melanoma cell-secreted exosomal miR-106b-5p may serve as a diagnostic indicator and potential therapeutic target in melanoma patients.

Long noncoding RNA MIR4435-2HG promotes hepatocellular carcinoma proliferation and metastasis through the miR-22-3p/YWHAZ axis.

Long noncoding RNAs (lncRNAs) play the critical biological role in many malignant tumours. MIR4435-2HG has been proven to be a novel oncogenic lncRNA. However, the exact role and mechanism of MIR4435-2HG in hepatocellular carcinoma (HCC) remain unclear. Here, we found that MIR4435-2HG is overexpressed in HCC tissue compared to normal controls and that high level of MIR4435-2HG indicates a poorer prognosis in HCC patients. MIR4435-2HG enhances the growth and metastasis ability of HCC cells. MIR4435-2HG promotes the expression of YWHAZ by sponging miR-22-3p to liberate YWHAZ mRNA transcripts. MIR4435-2HG facilitates the proliferation and metastasis of HCC by modulating the miR-22-3p/YWHAZ axis. These results demonstrated the role and mechanism of MIR4435-2HG in malignant progression of HCC. MIR4435-2HG may be used as the prognostic marker and treatment target for the patient with HCC.

Long non-coding RNA LINC00520 promotes the proliferation and metastasis of malignant melanoma by inducing the miR-125b-5p/EIF5A2 axis.

BACKGROUND: Long intergenic non-protein coding RNA 520 (LINC00520), a novel identified lncRNA, has been shown to modulate the malignant phenotype of tumor cells in some malignant tumors. However, the exact role and molecular mechanism of LINC00520 in malignant melanoma has not been studied. METHODS: The expression of LINC00520 in melanoma tissues were detected by using RNA-seq analysis and qRT-PCR. Melanoma cases from the public databases (The Cancer Genome Atlas (TCGA), GEO#GSE15605, GEO#GSE34460 and GEO#GSE24996) were included in this study. CCK-8 assay, EdU assay, transwell and scratch wound assay were used to explore the role of LINC00520 in melanoma cells. Luciferase reporter assays, MS2-RIP, RNA pull-down and RNA-ChIP assay were used to demonstrate the molecular biological mechanism of LINC00520 in melanoma. RESULTS: We found that LICN00520 was found to be overexpressed in melanoma tissue. High expression of LICN00520 is a risk factor for the prognosis of melanoma patients. LINC00520 promotes the proliferation, invasion and migration of melanoma cells. LICN00520 exerted its oncogenic role by competitive binding miR-125b-5p to promote Eukaryotic initiation factor 5A2 (EIF5A2) expression. We also showed that LICN00520 promotes the growth and metastasis of melanoma in vivo through regulating miR-125b-5p/EIF5A2 axis. CONCLUSIONS: All results elucidated the role and molecular mechanism of LINC00520 in the malignant development of melanoma. LINC00520, a new oncogene in melanoma, maybe serve as a survival biomarkers or therapeutic target for melanoma patients.

Long non-coding RNA ZEB1-AS1 promotes colon adenocarcinoma malignant progression via miR-455-3p/PAK2 axis.

OBJECTIVE: The long non-coding RNA zinc finger E-box-binding homeobox 1 antisense 1 (ZEB1-AS1) acts as an oncogenic regulator in many human tumours. In the present study, we identify the role and potential molecular biological mechanisms of ZEB1-AS1 in colon adenocarcinoma (COAD). METHODS: QRT-PCR was used to detect the expression of ZEB1-AS1, miR-455-3p and p21-activated kinases 2 (PAK2) in COAD tissues. CCK8 assay, EdU assay, transwell assay and scratch wound assay were used to explore the biological function of ZEB1-AS1 in COAD cells. Bioinformatics, luciferase reporter assays and an RNA pull-down assay were used to demonstrate the mechanism of ZEB1-AS1. We further explore the role of ZEB1-AS1 in vivo though xenograft tumour assay. RESULTS: We found that ZEB1-AS1 expression was significantly up-regulated in COAD tissues, and high ZEB1-AS1 level was correlated with the poor prognosis of COAD patients. MiR-455-3p plays an anti-cancer role in COAD by targeting PAK2. We confirmed that ZEB1-AS1 promotes PAK2 expression by sponging miR-455-3p, thus facilitating COAD cell growth and metastasis. CONCLUSIONS: To sum up, this result illustrates the novel molecular mechanism of ZEB1-AS1 in COAD and provides a new target for the diagnosis and treatment of COAD patients.

Next-generation sequencing reveals hsa_circ_0058092 being a potential oncogene candidate involved in gastric cancer.

Gastric cancer is a serious problem for human health. As part of noncoding RNA, circular RNA (circRNA) plays a key role in the occurrence and development of malignant tumor. We used next generation sequencing technology to detect circRNA expression profiles in 5 paired human gastric cancer tissues. Then, bioinformatics analysis was carried out to analyze the function of dysregulated circRNAs. Hsa_circ_0058092 was selected as the object of follow-up analysis. After using the Cistrome DB dataset the data was used to predict specific transcription factors of hsa_circ_0058092. The relationship between hsa_circ_0058092 and PODXL was further validated using RT-PCR and immunohistochemical techniques. Survival data were collected using a Kaplan-Meier analysis of hsa_circ_0058092. We identified 319 aberrantly expressed circRNAs, Hsa_circ_0058092 was selected for our studies. Functional analysis of hsa_circ_0058092 revealed that it was related to metabolic processes. The prediction results suggested that hsa_circ_0058092 has a relationship with hsa-miR-4269 which could specifically bind to the PODXL sequence. Transcription factor CEBPB may regulate the transcription process of hsa_circ_0058092. The expression of hsa_circ_0058092 was positively correlated with PODXL expression. Immunohistochemical analysis of PODXL showed that the expression of PODXL protein in cancer tissues is higher than that in adjacent tissues. Kaplan-Meier analysis suggested that hsa_circ_0058092 was associated with survival of gastric cancer patients. All of these results showed that hsa_circ_0058092 was a potential oncogene.

Long noncoding RNA LINC00518 acts as a competing endogenous RNA to promote the metastasis of malignant melanoma via miR-204-5p/AP1S2 axis.

Long intergenic nonprotein coding RNA 518 (LINC00518) has been shown to promote cancer cell growth and metastasis in some human tumors. Although it has been reported that LINC00518 is dysregulated in melanoma, its exact role and molecular mechanism in melanoma remain unclear. RNA-seq analysis and qRT-PCR was used to detect the expression of LINC00518 in melanoma tissues. Melanoma cases from The Cancer Genome Atlas (TCGA), GEO#GSE15605 and GEO#GSE24469 were included in this study. 3D migration, transwell and scratch wound assay were used to explore the role of LINC00518 in melanoma cells. Bioinformatics, luciferase reporter assays, MS2-RIP assay, RNA pull-down assay and RNA-ChIP assay were used to demonstrate the mechanism of LINC00518 in melanoma. We found that LICN00518 was significantly upregulated in melanoma tissue, and high LICN00518 level was an independent risk factor for melanoma patients. LICN00518 promoted the invasion and migration of melanoma cells. LICN00518 exerted its role by decoying miR-204-5p to upregulate Adaptor Related Protein Complex 1 Sigma 2 Subunit (AP1S2) expression. We also demonstrated that LICN00518 promoted melanoma metastasis in vivo through pulmonary metastasis assay. This result elucidates a new mechanism for LICN00518 in the metastasis of melanoma. LICN00518 may serve as a survival indicator and potential therapeutic target in melanoma patients.

Long noncoding RNA OIP5-AS1 acts as a competing endogenous RNA to promote glutamine catabolism and malignant melanoma growth by sponging miR-217.

The long noncoding RNA (lncRNA) OIP5-AS1 has been considered to promote the growth and metastasis of many human tumors. However, the role of OIP5-AS1 in melanoma has not been reported. In this study, we found that OIP5-AS1 levels were significantly elevated in melanoma tissue and that high OIP5-AS1 expression was an independent risk factor for the poor survival of patients with melanoma. miR-217 suppressed glutamine catabolism in melanoma cells by targeting glutaminase (GLS), the rate-limiting enzyme of glutamine catabolism. We also demonstrated that OIP5-AS1 acted as a sponge of miR-217 to upregulate GLS expression, thus promoting glutamine catabolism and melanoma growth. Overall, this result elucidates a new mechanism for OIP5-AS1 in metabolism in melanoma and provides a potential therapeutic target for patients with melanoma.

circRNA_0084043 promote malignant melanoma progression via miR-153-3p/Snail axis.

Circular RNAs (circRNAs) has been found to play an important role in the regulation of multiple diseases, and participate in cancer development. However, the role of circRNA in malignant melanoma has not been reported. In this study, human circRNA microarray was used to screen the dysregulated circRNA in melanoma. We found that circRNA_0084043 was significantly up-regulated in melanoma tissue, and the result was replicated in a larger sample size. High circRNA_0084043 expression was an independent risk factor of overall survival in melanoma patients. circRNA_0084043 promotes melanoma cell proliferation, invasion and migration. Bioinformatics and luciferase reporter assays confirmed that circRNA_0084043 directly binds to miR-153-3p, and Snail is directly targeted by miR-153-3p. We also demonstrated that circRNA_0084043 may act as the sponge of miR-153-3p to up-regulate Snail expression, and consequently function as an oncogene in melanoma. Overall, this result elucidates a new mechanism for circRNA_0084043 in melanoma development and provides a potential therapeutic target for melanoma patients.

Long non-coding RNA H19 promotes glucose metabolism and cell growth in malignant melanoma via miR-106a-5p/E2F3 axis.

PURPOSE: lncRNA H19 has been considered as an oncogenic lncRNA in many human tumours. In the present study, we identify the role and molecular mechanism of lncRNA H19 in melanoma. METHOD: QRT-PCR was used to detect the expression of lncRNA H19 and E2F3 was detected in melanoma tissues. Cell counting kit-8 (CCK8), representative metabolites analysis was used to explore the biological function of lncRNA H19, miR-106a-5p and E2F3 in melanoma cells. Bioinformatics, luciferase reporter assays, MS2-RIP and RNA pull-down assay was used to demonstrate the molecular mechanism of lncRNA H19 in melanoma. We further test the function of lncRNA H19 in vivo though Xenograft tumour assay. RESULTS: We found that lncRNA H19 was increased in melanoma tissue, and lncRNA H19 was correlated with poor prognosis of melanoma patients. miR-106a-5p acts as a tumour suppressor in melanoma by targeting E2F3. E2F3 affects the melanoma cell glucose metabolism and growth. We also demonstrated that lncRNA H19 may function as the sponge of miR-106a-5p to up-regulate E2F3 expression, and consequently promote the glucose metabolism and growth of melanoma. CONCLUSIONS: This result elucidates a new mechanism for lncRNA H19 in melanoma development and provides a survival indicator and potential therapeutic target for melanoma patients.

miR-137 inhibits glutamine catabolism and growth of malignant melanoma by targeting glutaminase.

Glutamine catabolism is considered to be an important metabolic pathway for cancer cells. Glutaminase (GLS) is the important rate-limiting enzyme of glutamine catabolism. miR-137 functions as a tumor suppressor in many human malignant tumors. However, the role and molecular mechanism of miR-137 and GLS in malignant melanoma has not been reported. In this study, we showed that miR-137 was decreased in melanoma tissue, and the low miR-137 level and high GLS expression are independent risk factor in melanoma. miR-137 suppressed the proliferation and glutamine catabolism of melanoma cells. GLS is crucial for glutamine catabolism and growth of malignant melanoma. We also demonstrated that miR-137 acts as a tumor suppressor in melanoma by targeting GLS. This result elucidates a new mechanism for miR-137 in melanoma development and provides a survival indicator and potential therapeutic target for melanoma patients.